Available online at www.ijpcr.com International Journal of Pharmaceutical and Clinical Research 2014; 6(3): 192-195 ISSN- 0975 1556 *Author for correspondence: E-mail: sshrmany@yahoo.co.uk Research Article Sickle Cell Anemia in Relation to Total Homocysteine Levels and the Role of Anticoagulant Proteins Mohammed Al-Nuzaily¹, *Faisal Ali² ¹Haematology Department, Faculty of Medicine and Health Sciences, Sana a University, Yemen ²Haematology Department, Kuwait University Hospital, Faculty of Medicine and Health Sciences, Sana a University, Yemen Available online: 1 st July 2014 ABSTRACT Sickle cell disease (SCD) is a genetic disease characterized by hypercoagulable state and increased risk of thromboembolic events, a rare but significant complication of SCD. Protein C and S are natural anticoagulant proteins. Total homocysteine (tHcy) is an independent risk factor for venous thromboembolism and cardiovascular disease, and its level is therefore of interest in sickle cell disease. The aim of this study was to investigate the plasma levels of protein C and S levels and their relationship to homocysteine level in patients with sickle cell anemia compared to control subjects. In this study twenty patients (m=12, f=8) with sickle cell anemia, classified into sickle cell trait (Hb AS, n=15) and sickle cell disease (Hb SS, n=5), and twenty normal age-sex controls (m=12, f=8) were included. Protein C, S and homocysteine levels were measured using ELISA diagnostic kits technique. The data was statistically analysed by SPSS- 17 and p values less than 0.05 were considered significant. Our results showed that mean tHcy levels were found to be significantly higher in patients (SS and/or AS) than in control group. No significant correlation was observed between tHcy with protein C or S. The mean value of protein C and S within normal range and statistically not signi ficant in patients compared to controls, but significantly decreased in Hb SS patients. In conclusion, sickle cell anemia is associated with mild elevated tHcy level which may contribute to increased risk of hypercoagulability and thromboembolic complications. Keywords: sickle cell disease; thromboembolism; protein C and S; homocysteine INTRODUCTION Sickle cell disease (SCD) is a genetic disease characterized by hypercoagulable state in which various hemostatic systems both in steady state and during vaso- occlusion are perturbed with increased activation of the coagulation system and platelets, thrombin generation, and occurrence of thrombosis 1-4 . The pathogenesis of hypercoagulability is considered to be multifactorial. Altered components of hemostasis system in SCD have been suggested. Low plasma levels of protein C, protein S, and antithrombin III, elevated plasma levels of thrombin-antithrombin (TAT) complexes, prothrombin fragment 1+2 (F1+2), D-dimer complexes, and circulating antiphospholipid antibodies, platelet activation during vaso-occlusive crisis, abnormal external exposure of phosphatidylserine (PS) and adherence of sickle erythrocytes to the vascular endothelium, reducing NO level in the presence of hemolytic anemia, and increased tissue factor expression have been detected in SCD patients 5,6 . These abnormalities of hemostatic system in SCD are leading to increase risk of thrombosis. Total homocysteine (tHcy) is an independent risk factor for venous thromboembolism and cardiovascular disease 7,10 . Homocysteine has often been shown to be related to occlusive vascular disease independently of other known risk factors 11 . Platelet aggregation, anticoagulant functions of plasma and vascular vasomotor function are altered in the presence of high plasma levels of Hcy 12 . Homocysteine may inhibit thrombomodulin 13 and protein C, S may be reduced in SS disease 14 . Therefore, it is possible that raised homocysteine levels in SS disease predispose to the development of thrombosis 15 through inhibition of the protein C anticoagulant pathway 16 . Furthermore, thrombosis may contribute to the pathogenesis of several SCD-related complications. For example, stroke, caused by large vessel obstruction with superimposed thrombosis, often occurs in SCD patients 17 . Both pulmonary embolism and pregnancy- related venous thromboembolism appear to occur more commonly in SCD patients than in appropriate control patients 18’19 . Protein C and S are vitamin K-dependent protein with an essential natural anticoagulant functions. Protein C exists in an inactive form and is activated by thrombin- thrombomodulin complex. It’s activated form (activated protein C, APC) controls the coagulation process by cleaving and inactivating factor VIIIa (FVIIIa) and FVa in the presence of protein S, which act as a cofactor for